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S U M M E R 2 0 1 7 U o f L M A G A Z I N E | 3 3 A WIDER LOOK Groundbreaking research in the understanding of gut microbes' role in health and disease also is being conducted in other departments at UofL, including: • Robert Friedland, professor in the Department of Neurology, led an international group of researchers that was the first in the world to establish a link between gut microbiota and neurodegenera- tion. In 2016, he published research demonstrating that exposure to misfolded proteins produced by E. Coli in the gut leads to misfolded proteins in the brain characteristic of neurodegenerative diseases. • Craig McClain, Shirish Barve, and Wenke Feng, PhD, in the Division of Gastroenterology, Hepatology and Nutrition, are studying the relationship between gut microbiota and alcoholic liver disease. • Scott Whittemore, director of the Kentucky Spinal Cord Injury Research Center, is working with Barve to understand how spinal cord injury affects the gut microbiota, resulting in inflammation and health consequences elsewhere in the body. • Jason Chesney, director of the James Graham Brown Cancer Center, is studying a novel class of immunotherapies, immune checkpoint inhibitors, that is reducing death rates in several types of cancer. He believes a patient's gut microbiota may dictate resistance or responsiveness to these immune checkpoint inhibitors. raises hope that we can target those mechanisms to prevent severity of the disease." BUILDING RESOURCES FOR FUTURE RESEARCH Given the significance and therapeutic potential of this area of research, UofL has committed to invest- ing in research infrastructure and supportive data. To facilitate a greater understanding of the interrelationship of gender, age, diet, socioeco- nomic status and the structure of an individual's microbiota, Nejat Egilmez, chair of the Department of M&I, along with Richard Lamont, chair of the Department of Oral Immunology and Infectious Disease in the School of Dentistry, and Riaan Van Zyl, associate dean for research at Kent School of Social Work, are leading a 21st Century University Initiative project, funded by UofL, to compile a mi- crobiota data repository. The three-year project involves collecting microbiota samples along with social and health information from thousands of individuals into a database for future research. "The discovery of a link between commensal microbiota and health is a major paradigm shift in medicine," Egilmez said. "The UofL initiative is not only timely but extends the current paradigm into the social arena, investigating a potential link between social determinants and the microbiome- health axis. This database will not only be a valu- able resource for the university, but could benefit researchers across the nation and the world." In addition, Bodduluri and Jala are working to establish a functional microbiomics core research facility at UofL. Existing state-of-the-art capabilities in gene sequencing will be augmented with a center for raising germ-free mice, those that have no mi- crobes in their system, and maintaining gnotobiotic mice, those with a well-defined set of microbes. An anaerobic culture facility for growing microorgan- isms that require an oxygen-free environment will allow the germ-free mice to be colonized with specific microbes, enabling the researchers to more thoroughly study the effects and functions of indi- vidual bacteria and develop potential therapies. For the researchers, sorting out the gut's inhabit- ants and their roles is an epic task, but the potential rewards are invaluable. "We are really excited about this line of work. It is just starting and has tremendous potential," Bodduluri said. Researchers Nathan Schmidt, Michele Kosiewicz, Haribabu Bodduluri, Venkatakrishna Jala and Nejat Egilmez.

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